WO2017069818A1 - Dual-chamber syringe and associated connecting systems - Google Patents

Abstract

A dual-chamber syringe system is disclosed. Critical system oriented elements are disclosed, including plunger valve designs for accurate measurement and true, non-canting displacement; tamper and inadvertent valve actuation indicators, as well as, valve status 5 indicators; anti-reflux construction; novel indicia patterns for dual-chamber syringe operation; structure and method for quality assurance that no gas can be delivered from a proximal chamber of the dual-chamber syringe and a kit for single step dose transfer. In addition, a tapered fitting valve is disclosed. The tapered fitting valve comprises a single molded incompressible, but supple part and a skeletal support whereby the tapered fitting 10 valve is opened by insertion into a tapered fitting. The preferred embodiment of an actuator portion of the valve is elliptical in shape.

Description

DUAL-CHAMBER SYRINGE AND ASSOCIATED CONNECTING SYSTEMS

Continuity

This application s a Contimiation-in-Part of U.S. Patent Application Serial No.:

14/121 ,681 filed October % 2014 and titled COMPONENTS AND DEVICES FOR CLOSED MEDICAL SYSTEM: OPERATIO by Gale H. Thome (referenced, hereafter as Thome 681) which is a Continuation-in-Part of U.S. Patent Application Serial Number 13/872,828, filed April 29, 2013 and titled TWISTED SLIT VALVE filed by Gale H. Thome (referenced hereafter as I^'horne 828) and, further, a Continuation-in-Part of U.S. Patent Application Serial Number 13/068,529 filed May 13, 201 1 by Gale H. Thome, et al mid titled PRESSURE, ACTUATED VALVE FOR MULTI-CHAMBER SYRINGE APPLICATIONS (hereafter referenced as Thome 529), contents of each of which are made part hereof, by reference. Field of Invention

This application relates to dual-chamber syringes and more particular to syringes having conventional barrels of substantially constant diameter divided into two chambers by one or more plunger valves which are normally closed and selecti vely opened to dispense liquids from a more proximal chamber distally. Preferably, syringes used within the scope of the instant inventions comprise conventional barrels of consistent diameter along the length of such. Further, this application relates to novel valves for tapered fittings and methods which are formulated to improve efficacy and safety of dual-chamber syringes in medical practice.

Background

Disclosures of U.S. Patent 7,789,862 issued to Gale H. Thome, Jr. et al September 7, 2010, and other related U.S. Patent Applications describe separating a conventional syringe barrel into two chambers via a plunger valve having a displaceable stem. However, none of the disclosures treat critical system factors associated, with placing a diniS -chamber syringe system in commerce. Not only is a dual-chamber syringe required to keep fluids in each chamber of the syringe disparate and deliver onl y liquid chamber contents sequentially, but other concerns and factors must be considered to make a dual-chamber syringe system viabie. A number of system responses to those concerns and factors yield novel methods and devices as pari of the system disclosure disclosed herein.

As disclosed in referenced U.S. Patent Applications from which this disclosure continues, dual-chamber syringes commonly comprise a plunger valve which is nomially closed and selectively opened for transmitting fluids from a disparate chamber within the syringe. However, in medical practice, dual-chamber device efficacy and safety requires more to be considered than simply the valve and valve actuation alone, although the valve and selective chamber disparateness are critical parameters. As a system, the following operational parameters should be duly considered:

1. accuracy of measurement of dispensed dose

2. a tamper-evident indicator to provide assurance that system is ready

3. certainty of valve actuation only at a desired point in a medical procedure

4. assurance that no back-flow or reflux occurs as dispensing is completed

5. indicia provided upon the barrel of the syringe clearly depicts needed

information and is neither confusing nor perplexing

6. monitoring of cri tical safety parameters

7. compatibility with preferred sterilization procedure

8. number of fluid transfer steps required to fi ll or mix liquids in a distal chamber

9. closed system operation when handling hazardous or air sensitive materials Safety and efficacy of dual- chamber syringe operation is as much dependent upon the above considerations as a properly operating plunger valve. Such parameter may require different parameter considerations for different modes of plunger valve actuation as is disclosed in detail hereafter.

easurement Accuracy

With a properl operating plunger valve, there are two conditions which affect measurement accuracy. The first is assurance that all fluid is expelled from a first dispensing chamber before an associated plunger valve is opened to dispense fluid from a second chamber. The second is more critical, because, in conventional syringe operation,

measurement of successive volume dispensed is communicated from a plunger through a barrel having indicia marked to measure plunger displacement. As a plunger in a dual- chamber syringe is not mechanically affixed to a stabilizing stem and is, therefore, displaced only by force of fluid within a syringe barrel and variously retarded by internal barrel friction, it is critical that the plunger displacement be "true" and that the plunger not cant during displacement because such canting, though insufficient to permit fluid flow between

chambers, cou!d result in inaccurate volumetric measurement due to linear angular displacement of the pl unger val ve to barrel ali gnmen t.

Tamper. Evidence

Improper handling of a dual-chamber syringe device can actuate a val ve prematurely, resulting in untimely mixing of dose chamber fluid with fluid in a proximal chamber. A tamper evident indicator would preclude using a syringe having such a problem.

Valve Actuation

A plunger valve, opened by displacement of an associated stem, can be inadvertently actuated by inadvertent undue displacement of the plunger valve during a filling process. As stated supra, premature valve actuation can result in mixing of fluids which should otherwise remain disparate. It is also desirable for a clinician to know when a drug dose has been delivered and a following delivery of a flushing liquid has begun.

Reflux

Dual-chamber syringes provide a unique opportunity for reflux occurring not at the end of delivery of fluid from a first of distal chamber, but upon final delivery from the upstream or more proximal chamber- Such reflux may be somewhat curtailed by pressurized air remaining in the proximal chamber, but, more likely, slower to recover compression of elastic members associated with the proximal chamber can result in a negative pressure relative to downstream fluids and resultant reflux. Such reflux is highly undesirable in patient catheter lines and in other applications where retrograde flow can cause blockage. In U.S. Patent 7,789,862 reflux is taught to be assuaged by gas pressure resident in a rear ehamber upon final dispensing ofliquid therefrom. However, careful analysis of dynamics of actions which generate reflu show that pressure reduction in the rear- chamber occurs too rapidly when compared to reflux producing mechanical structure within the chamber to effectively arrest all reflux.

indicia

Measurement indicia must clearly provide for not only distal chamber volumetric determinations, but for accurate proximal chamber determinations, as well, Further, because of the likelihood of the proximal ehamber being pre-tilled, volumetric and other identifying indicia are also needed. Because there are two plungers in a dual-chamber syringe and two associated chambers for which volumes should be accurately measured, a number of indicia patterns are possible. Some of the possibilities place special requirements on filling and other factors such as a maximum volume of gas which can be stored in a proximal chamber. .Safety Monitoring.

It is standard practice to purge all gas from a syrmge prior to dispensing liquid therefrom. While such can be accomplished in a single (conventional) syringe, a dual- chamber syringe may have gas disposed in the proximal chamber due to fi lling procedures or ontgassing. Of course, a plunger valve for a dual-chamber syringe should be designed to separate gas from liquid for a liquid only delivery, such as provided by a liquid only zone device. However, for quality assurance purposes, a control check should be provided for both manufacturing and user testing.

Sterilization Procedure .Compatibility

Presently preferred sterilization of pre-filled syringes is by gamma, radiation. For this reason all materials, particularly those which are used to form the syringe barrel, vaive plunger and stem and plunger and plunger rod, should be selected to be unaffected or at least predictably affected and not operationally impaired thereby.

Fluid Transfer Methods and Apparatus

In such applications as PiXUS storage and retrieval, a system comprising a dual- chamber syringe may profitably enclose both a dual-chamber syringe and an associated distal chamber fluid containing vessel in the same package. Conventionally, if both the syringe and vessel comprise male luer fittings, a female/female luer connector is employed. However, introduction of an additional component adds steps and introduces former opportunity for contamination.

Closed System Operation

There are many reasons for keeping a system closed during a medical procedure (e.g. handlin hazardous drugs or air sensitive materials). A male luer fittin of a medical syringe is inherently open when disconnected from a female fitting. For this reason, needleless connectors and male adapters are commonly employed in oncology drug delivery. However, as considered for Fluid Transfer, supra, such generally requires additional components, steps and associated cost.

General

While the above disclosed considerations apply generally to dual-chamber syringes, it is considered prudent to provide an opportunity for evaluating these considerations across a spectrum of dual -chamber syringe designs. In addition, a syringe having structure for an integrally affixed tapered valve is also provided.

Definitions for Terms Used

assembl n: a device which is made from at least two interconnected parts

barrel/?: a cylindiica! elongated portion of a conventional syringe which is substantially of constant diameter along a long axis of the syringe, open on one end to receive a plunger tip and plunger rod assembly used for displacing fluid within the barrel and partially closed at an opposite end except for an orifice or portal through which Quid is ejected or aspirated chamber n: a disparate volumetric portion of a divided barrel

conventional adj: sanctioned by general custom; i.e. commonplace, ordinary

disparate n when used to describe a first volume o contents relative to another volume of contents, the first volume of conients being kept distinctly separate from the other volume of contents

differential pressure (ΔΡ) »: a pressure gradient resulting from unequal pressures exerted upon opposing sides of a structure; generally as used herein, M*™ P_p - P_d, where subscript "p" represents proximal and subscript "d" represents distal.

distal adj: a term which depicts placement away from a reference point (e.g. away from a user of a syringe)

downstream adj: a direction which is consistent with flow out of a syringe or away from a user

fluid «: a substance (e.g. a liquid or gas) which tends to take the shape of a container front adj/n: when referenced to a syringe, a distally disposed or a distally disposed she (e.g. a front of a syringe comprises the commonly provided liier fitting and associated, orifice) gas n: a fluid which is neither solid nor liquid

liquid »: a fluid which is neither solid nor gaseous, free flowing like water liquid only zone «: a space within a syringe barrel which can only be physically occupied by liquid (see Thome 862)

medial dj: occurring away from an outer edge; disposed near the center of (e.g. disposed away from an edge or periphery and in the vicinity of a center of gravity or axis of symmetry) plunger rod a port ion of a syringe piston apparatus, usually affixed to a plunger tip, to which force is applied to displace fluid within a syringe barrel

plunger n: a portion of a part that divides a syringe barrel into two disparate fore and aft chambers.

prime v: to completely .fill liquid into a cavity generally by removing air therefrom (e.g. priming a gas separator)

proximal adj: opposite of distal (e.g. a terra which depicts placement nearer to a reference point)

rem adj opposite from front (i.e. generally associated with a part of a syringe barrel which is proximal to a syringe user relative to an outflow orifice)

reflux n: type of retrograde (upstream) flow relative to a direction of dispensing, usually resulting from energy stored in flow-producing parts of a syringe and usually undesired state n a mode or condition of matter, e.g. gaseous, liquid or solid or of a device, such as an open state of a valve

stiction n a special case of friction; stiction being related to the force required to initiate motion to a resting body, esp. when that force is greater than friction associated with a moving body

stop n: an obstruction which is differentiated from friction or stiction which halts

displacement of a stopper or plunger without retrograde motion

S stopper n: a plug

substantially a dv : to a most reasonably achievable amount syringe n : a medical device used for injecting or withdrawing fluids, a syringe usually comprising a plunger and plunger rod disposed to be displaced within a conventional cyiindrical syringe barrel and. for a dual-chamber swinge, includes a plunger valve t provid the dual-chamber syringe

Table I

BRIEF SUMMARY AND OBJECTS OF THE INVENTION In brief summary, the novel inventions disclosed herein, while having broader applications, alleviates known problems related to providing commercially viable dual- chamber syringe systems. Dual-chamber syringes for such systems preferably comprise a conventional syringe barrel having a substantially uniform internal cylindrical barrel divided into two disparate chambers (proximal and distal) by a plunger valve, which is normally closed. In particular, as an example of a dual-chamber syringe for such systems, such a syringe comprises a plunger valve having a stem which is displaced by collision with the distal end of the syringe following a distal chamber dispensing cycle. The col lision opens the valve for disparately dispensing contents from the proximal chamber, it should be recognized that gas can be discharged from the distal chamber in the manner generally employed in conventional syringe use. Any gas residing in the proximal chamber is trapped and retained therein such that no gas is delivered from the proximal chamber. The following summary is organized to provide disclosure of novel methods and apparatus which provide solutions for problems listed for the operational parameters cited above:

Accuracy of measurement of dispensed dose

In con ventional syringe use, metering of a dispensed or drawn dose is dependent upon visually interrelating the distal edge of a plunger with indicia on the exterior of a syringe barrel. It is well known in medical syringe art that canting of a plunger results in

misalignment between plunger edge and indicia Sines making measurement less accurate. In conventional syringes, canting is impeded by plunger rod to plunger assembly structure. However, an unattached fluid driven plunder, such as the chamber separating plunger in a dual-chamber syringe, must be canting free for other reasons.

A ring (306), proximaliy disposed in a plunger valve to obviate canting, is disclosed in US Patent 7,789,862. However, a ring is a separate part which adds to the overall cost of the dual-chamber syringe in which it is employed. A novel approach as part of the instant invention comprises structure within the proximal part of the plunger valve which provides sufficient space for gas capture and retention, while providing suitable support for the proximal portion of the val ve to retard canting. In the preferred embodiment, the support is afforded by a plurality of joined tubes which communicate the support to the circumference of the valve while providing a necessary volume for gas capacity. In addition to resisting canting, such rear support also precludes departure of outer cylindrical portions of the associated plunger from the inner surface of the barrel which would otherwise result in liquid communicating within the plunger to barrel interface, a condition which is highly undesirable.

Tamper-evident indication

Tamper evidence h generally provided as a visual indicator. The greatest effect of operational tampering in a dual-chamber syringe is premature actuation of an associated plunger valve. To make actuation more evident, only a portion of an associated plunger valve stem is visibly see on the distal side of a non-actuated plunger valv and only an extended end of the stem is seen on the proximal end of an actuated val ve. Whi le this is noticeable as a tamper-evident indicator, it is also an indicator of proper valve switching during a liquid dispensing procedure.

Reflux Inhibition

Generally reflux in a medical line (such as a catheter) is the consequence of upstream directed flow resulting irom compression followed by relaxation of elastic parts, generally at the end of a delivery cycle of fluid from a proximal chamber of the dual-chamber syringe. Of course, one skilled in catheter deliver)' art understands that such upstream flow brings body fluids into the line which is generally negatively consequential.

In a dual-chamber syringe system involving a displaeeable syringe stem for opening a fluid conduit to a liquid only zone, two novel approaches provide assurance against reflux. In a first approach, a stem having a length and geometry which provides for resetting the stem to close the valve and conduit pathway from the liquid only zone is effective in stopping further reflu as the valve is closed and pressure downstream from the valve is generally greater than pressure at a discharge orifice. Also, it is recommended that the rear plunger which displaces the valve stem be designed to be unresilient and have distally disposed geometry to provide a hard stop against the proximal end of the plunger val ve stem to inhibit reflux resulting from flow stoppage by collision between the plunger valve stem and rear plunger rod.

Another approach involves using an inflexible interface between a shoulder on a plunger rod stem and a proximal edge of the associated syringe. As deliverable liquid volume is predetermined in the dual-chamber syringe of this example of a dual-chamber syringe, a hard stop provided by the shoulder on the plunger rod colliding with the proximal end of the dual chamber syringe barrel is effective in inhibiting plunger motion which would cause reflux. Interestingly, presence of gas in the proximal chamber is still pressurized when a hard stop, following pressurized dispensing by force against the plunger rod is terminated by the collision. Relief of the pressure of the gas provides a continued gradual downstream liquid flow rather than reflux. easurement Indicia

In a dual-chamber syringe, indicia is needed for volumetric metering of contents of both the distai and proximal chambers. In a conventional single chamber syringe indica lines generally represent measurements of volumes to a fluid dispensing end. Length of indicia lines is commonly varied to provide visual discernment of major volume divisions. Four modes of volumetric measurement are provided. Note that, it should be the intent of design of devices made according to this invention to follow ISO guidelines for indicia, although there is no clear ISO specification related to dual-chamber syringes for proximal chamber and distal chamber content disclosure.

A first mode provides separate sets of indicia for metering each chamber (i.e. distal and proximal) and depends upon using each of the two plungers for measurement One set provides a measurement whic is limited on the pro imal end by the maximum dose or distal chamber volume. As an example. In a 35 ml syringe, 20 ml may be allocated to dose volume (distal chamber) and 10 ml dedicated to a flush volume (proximai chamber). The 5 ml disparity between the sum of volume in the two chambers and syringe design volume provides space for the valve plunger and safety capaci ty for trapped and retained, gas.

A second set of indica also utilizes both plungers for measuring and provides a measurement delineating from a point at which the reflux stop ends distal progress of the rear plunger prox imal to an indication of maximum volume of the proximal chamber. Other indicia can provide such information as total provided volume and identification of type and concentration of liquid in the proximal chamber.

A second mode provides a common set of indicia lines for both chambers, providing a more customary representation of lines for a user, with volumetric numbering disposed on one side for the distai chamber and on the other side for proximal chamber. Similar allocations for distal and proximal chambers and allowance for valve and safety gas retention volumes as disclosed for the first set of indicia.

A third mode provides indicia disposed upon a plunger rod which is displaced to serially displace bot plunger in a dual-chamber syringe. Onl one contiguous column of indicia is required, with indicia provided in reverse order to thai of a conventional syringe indicia indicating each respective unit of volume is numerical ly reduced proxiinally, thus indicating amount of fluid volume left in a referenced chamber. A reference Sine of measuremen t is between a proximal surface of syringe flanges and the respective sur face marking on the plunger rod. For such a mode to be safe and effective, a know and fixed relationship must exist within required measurement accuracy of the syringe between the location of the plunger indicia and length of the proximal chamber and enclosing elements. Advantage of this mode is that only a single column of indicia is required, although the requirement for a proximal chamber to be of fixed, known and predetermined length and expansion and contraction of a gas bubble inside the proximal chamber affecting chamber length must be considered.

A fourth mode also provides a single column of indicia, but in this mode the indicia are disposed on the surface of the barrel as in the case of^" a conventional syringe. Also, as in the case of the conventional syringe, measurement is by viewing a distal edge of the plunger associated with the plunger rod only. Of course, indicia, while in a single column and being continuous, must be displaced to account for volume of a plunger valve. The same conditions as required for the third mode also apply to this mode. .For such a mode to be safe and effective, a known and fixed relationship must exist within required measurement accuracy of the syringe between the location of the barrel indicia and length of the proximal chamber and enclosing elements. Advantage of this mode is that only a single column of indicia is required and measurement is made in the same way as for a single chamber syringe, although the reqtiiremeat for a proximal chamber to be of fixed, known and predetermined iength aad expansion and contraction of a gas bubble inside the proximal chamber affecting chamber Iength must be considered and assured to permit measurement within specified accuracy.

Quality and Safety Assurance

Other than the prescribed safety practice for syringes, a dual-chamber syringe has but one additional quality assurance consideration needed, it is critical thai no more gas than can be trapped and retained in the proximal chamber be therein. For a dual-chamber syringe valve which provides a closed conduit to a liquid only zone for liquid gas separation, a sure method for testing against too great a gas volume is performed with the simple steps of rotating the dual-chamber syringe such that the valve plunger is vertically disposed above the proximal chamber. When so disposed, gas must rise above the thus positioned bottom of the conduit. Both from a quality assurance standpoint and from a user test, safety of gas delivery prevention is assured when a line between the liquid and gas states is so disposed.

Sterilization Mode Compatibility

In past pre-filled syringe manufacture, it was common practice to fill syringes using sterile fill techniques. Recent FDA guidelines instruct use of gamma sterilization. To meet this requirement, only gamma stable synthetic resinous material comprising gamma stable polypropylene and butyl rubbers should be used for valve plungers, valve stems, barrels and plunger rod parts.

Complimentary Vessels and Interconnections

From a systems point of view, novel methods and combinations provide significantly improved products and techniques. While a dual-chamber syringe provides both opportunity to transport and deliver medicines in one chamber and a flush i a second chamber, long term storage of the wide variety of drugs likely requires extensive testing. Conv ersely, short term mixing and delivery of a wide variety of medicines in conventional single chamber syringes is commonly contemporarily practiced. The major advantage of a dual-chamber syringe over a single chamber syringe is commonly assessed as reduced requirements for interconnecting steps with associated user time and likelihood of contamination being prominent

considerations. From thi s point of vi ew, a source vessel , which provides liquid from a pre- filled syringe, having a complimentary fitting, such as a female luer fitting also significantly reduces assembly steps and, therefore, likelihood of contamination. For this reason, a novel provision for a female liquid source vessel provides a significant improvement in dual- chamber syringe safety and efficacy.

Closed Syringe Transfer System

Advantages of providing closed system transfer in a syringe is well known in hazardous drug handling art. Providing a syringe having a barrel which interfaces with a male adapter providing a valve which is only open when disposed within a femaie luer fitting provides a novel approach to constructing a dual-chamber syringe for closed system use. This novel invention comprises a tapered .fitting valve integrally affixed to a syringe having a skeletal interface for the valve molded as pari of the syringe barrel thereby replacing a conventional a male luer fitting of a syringe. Also a novel separate component which comprises the same novel valve construction as the syringe connected valve is disclosed, faventiye. Dual-Chaniber S

Accordingly, it is a primary object to provide novel dual -chamber syringe systems which incorporate one or more of the following novel objects:

It is a basic object to provide a dual-chamber syringe system comprising a plunger valve which does no cant and thereby distort barrel to plunger based indicia interpretation or result tn liquid flow within valve to barrel ring interface.

It is a very important object to provide readily seen tamper evident indicators which provide assurance of dual-chamber system integrity.

It is an elemental object to provide a dual-chamber syringe system which provides visual evidence thai an associated, plunger valve is in a closed state before actuation procedure and in an open state following actuation.

It is a fundamental object to provide a dual-chamber syringe system which comprises structure and parts which operate to inhibit reflux upon completing delivery from the proximal chamber.

It is an important object to provide for presentation of measurement indica for dual- chamber syringe operation which provides for systematic di ferentiation between chamber content and dispensing measurement and which provides indicators which are consistent with ISO standards.

It is a critical object to provide quality assurance indicators used to assure that gas resident in a proxima! chamber of a dual-chamber syringe is not greater than that which can be contained without delivery of gas from the syringe upon completing delivery from the proximal chamber.

It is a consequential object to provide a dual-chamber syringe universally comprising parts which are compatible with gamma sterilization.

it is an object to provide source liquid containers for use with a dual-chamber syringe system which reduce steps and time required for fluid transfer. It is a meaningful object to provide a syringe which comprises a skeletal support for a tapered fitting valve which replaces the male luer fitting conventionally placed on a syringe such that the support and valve provide a male luer fitting which oniy open when disposed in a female luer fitting,

It is another meaningful object to provide a male luer adapter as a separate component which employs structure of the tapered fitting valve.

These and other objects and features of the present invention will be apparent from the detailed description taken with reference to acco ipanyirig drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

Figure 1 Is an exploded perspective of a presently preferred embodimen t of a dual- chamber syringe made according to the instant Invention.

Figure 2 is a magnified side elevation of a val ve stem made according to the instant invention.

Figure 3 is a perspective of a valve plunger when disposed in a dual-chamber swinge.

Figure 3 A is a perspective of a valve plunger, similar to the valve plunger seen in Figure 3, but comprising a different hollow interior.

Figure 4 is a perspective of a valve stem disposed in a valv plunger such that a pathway in which the stem is disposed is closed to fluid flow.

Figure 5 is a perspective to the valve stem and plunger seen irs Figure 2 with the valve stem displaced to open the pathway to fluid flow.

Figures 6 i a cross section of an assembled dual-chamber syringe wherein a plunger valve divides a syringe barrel into two disparate chambers, both chambers being filled with liquid.

Figure 7 is a cross section of a dual-chamber syringe similar to the syringe seen in Figure 6 but rotated to provide a measurement of gas residing in the proximal chamber.

Figure S is a cross section of the dual-chamber syringe seen in Figure 7 syringe inverted to continue dispensing liquid from the distal chamber.

Figure 9 is a cross section of the dual-chamber syringe seen in Figure S with a distal portion of a stem impacting an inner surface of the barrel of the associated syringe.

Figure 10 is a cross section of the dual-chamber syringe seen in Figure 9 with the stem displaced such that the proximal portion of the stem is visible, such viability indicating actuation of the valve plunger to an open state. Figure 11 is a cross section of the dual-chamber syringe seen in. Figure 10 at the end of a proximal chamber dispensing cycle with farther displacement of a plunger rod being irapeded by collision of shoulders of the plunger rod with proximal portions of the syringe barrel.

Figure 12 is a side elevation of a syringe barrel for a dual-chamber syringe showing a pattern of indicia disposed on the outer surface of the barrel .

Figure 13 is a side elevation of a syringe barrel, similar to the barrel of Figure 12, but comprising an alternate indicia pattern.

Figure 13 A is a side elevation of a syringe barrel and associated plunger rod and plunger tip comprising indicia disposed on the plunger rod.

Figure 13B is a side elevation of a syringe barrel and plunger rod, similar to Figure 13 A, but with a pattern of indicia proximally disposed on the syringe barrel.

Figure 13C is a side elevation of a syringe barrel and plunger rod showing an indicia paitem which is similar to the paitem of Figure 13B, but specifically designed for flush and dose volumes different than those seen in Figure 13B.

Figure 130 is a side elevation of the swinge barrel and plunger rod seen in Figure 13C with a plunger valve and associated plunger rod tip displaced to empty a distal chamber.

Figure 13E is a side elevation of the syringe barrel and plunger rod seen in figure 13D with the plunger valve and plunger rod tip displaced to complete dispensing from a proximal chamber of the dual -chamber syringe.

Figure 13F is a side elevation of a dual-chamber syringe similar to the syringes seen, in Figures 13A-E. but with another indicia pattern.

Figure 14 is a perspective of a val ve for a tapered fitting with a medically disposed slit. Figure 15 is a perspective of a valve similar to the valve seen in Figure 14, but with a silt offset from a medial line (major axis of an ellipse).

Figure 16 is a perspective of the valve seen in Figure .15 with three intersecting planes disposed at the distal face, medial section and proximal face of the valve, respectively.

Figure 17 is a cross section of the valve seen in Figure 15 rotated to show disposition of an offset valve slit and a cavity disposed in a proximal portion of the valve.

Figure 17A is a cross section of the proximal end of the valve.

Figure 18 is a cross section of the proximal face of the valve seen in Figure 17.

Figure 39 is a cross section at a medial plane, seen in Figure 16, of the val ve seen in Figure 17.

Figure 20 is a cross section at a proximal plane, seen in Figure 16, of the valve seen in Figure 1 7.

Figure 21 is a cross section of the e!Hpticaliy shaped valve seen in Figure 18 compressed to a circular shape.

Figure 22 is a cross section of the elliptical ly shaped valve seen in Figure 1 compressed to a circular shape.

Figure 23 is a cross section of the ellipiicaJiy shaped valve seen in Figure 20

compressed to a circular shape.

Figure 24 is a cross section of the valve seen in Figure 1.7, rotated 90 degrees with a section taken in the plane of the slit and a skeletal support, seen in Figure 26 disposed to provide a brace for the valve.

Figure 25 is a cross section of a skeletal support for the valve seen in Figure 17.

Figure 26 is a cross section of the skeletal support seen in Figure 17, but rotated 90 Figure 27 is a frontal elevation of the skeletal support seen in Figure 25.

Figure 28 is a cross section of a male adapter device comprising a valve for a female tapered liter fitting.

Figure 29 is a cross section of the male adapter device seen in Figure 28, rotated 90 degrees.

Figure 30 is an exploded view of parts for a dual-chamber syringe having a barrel which is structured to em loy a valve for a tapered luer fitting.

Figure 31 is an exploded view of the parts seen in Figure 30 with a valve affixed to provide a male luer fitting for die dual-chamber syringe.

Figure 32 is a cross section of a fully assembled dual-chamber syringe with barrel affixed with the valve and compression ring.

Figure 33 is a magnified copy of the circled portion of the barrel seen in Figure 30.

Figure 34 is a magnified copy of the circled portion of the barrel seen in Figure 31.

Figure 35 is a magnified copy of the circled portion of the barrel seen in Figure 32.

Figure 36 is a perspective of a combination of a dual-chamber syringe and a female

DE TAILED DESCRIPTION OF THE ILLUS TRATED EMBODIMENTS

While the instant inventions disclosed herein are applicable to a wide variety of dual- chamber syringe applications and a number of tapered male/female insertion type fluid connectors, the detailed description provided herein is focused upon examples of medical de vices. In this description, the terra proximal is used to indicate thai segment of a device which is a closest part to an object of reference. The terra distal refers to an opposite orientation. Reference is now made to the embodiments illustrated in Figures 1 -36 wherein like numerals are used to designate like parts throughout and primes of numbers generally indicate parts which are similar in shape and or function of those numbers, but not exactly the same,

An Exemplar System

Seen in Figure 1 is an exploded view of parts which can be used to assemble a version of a dual-chamber syringe system 10, the parts being part of a system used to prepare and deliver medical preparations followed by a flushing liquid in a medical environment. While similar to art cited in the Continuity section provided supra, all but one of the parts, a plunger rod tip 20, has added novelty required for system's applications for dual-chamber syringes.

In additio to plunger rod tip 20, dual-chamber syringe system 10 comprises a rear plunger rod. 30 used to directly displace tip 20 and an associated plunger rod sleeve 32, a plunger 40 which is part of a normally closed valve, an actuating stem 50 which is disposed within a valved pathway of plunger 40 to form a plunger valve 70 and displaced to open a fluid pathway within plunger 40 thereby providing a normally closed valve, and a

conventional syringe barrel 60, Barrel 60 comprises a male luer lock fitting 62 for drawing and dispensing fluid. Application and need tor sleeve 32 is fully disclosed hereafter. A Fre-filled system

An assembled dual-chamber syringe system 10 is seen in Figure 8. Actuating stem 50 is displaced into plunger 40 to form plunger valve 70. A chamber 80 disposed between plunger valve (valve) 70 and plunger rod tip 20 contains a fluid 84 and is anticipated to comprise both a liquid 84 and a gas 86. It is preferred thai chamber 80 be pre-filled by a manufacturer before delivery to a site of use. As is well known in medical syringe use art, unless otherwise prescribed, only liquid should be dispensed from chamber 80 with all gas remaining resident in chamber 80 at the end of a chamber 80 dispensing cycle,

A second chamber 90, disposed between valve 70 and fitting 62, is kept disparate from chamber 80 for sequential fluid delivery by action of valve 70 as disclosed m detail hereafter. Fluid withdrawal and dispensing associated with chamber 80 is conducted by displacing plunger rod 30 in the same manner as fluid is manipulated in a conventional syringe and is performed prior to dispensing liquid from chamber 80.

Displaeeable stem plunger valve

A magnified view of stem 50 is seen in Figure 2. Generally, stem 50 comprises an enlarged footing 94 sized to collide wit syringe barrel 50 at a distal dispensing hole without inhibiting flow through the hole and a bulbous central portion 96 which is sized to obstruct the fluid pathway of plunger 40 when disposed therein. Between footing 94 and portion 96, stem 50 comprises a substantially constant diameter, linear extension 98 which leads to a conical segment 99. Bulbous portio 96 is shaped to be retained by compression within the valve plunger 40 pathway until stem displacement and compressive forces act to extricate stem 50 from the pathway. Once that condition occurs, the shape of conical segment 99 is acted upon by the interactive compressive forces associated with barrel 60 and plunger 40 to further expel bulbous portion 96 from the pathway, A channel 102 which is disposed along footing 94, extension. 98 and segment 99 provides an open passageway for fluid flow when bulbous portion 96 is outside the pathway.

Stem 50 further comprise a finned section 100 having a plurality of bJaded parts which provide for stability within the path way and a dear fluid path. Length of section 1.00 is an important dimension as disclosed in detail hereafter.

A magnified image of a proximal side of plunger 40 is seen in Figure 3. Similar plungers are disclosed in art from which U.S. Patent Application contmues-in-part However, plunger 40 does not require a separate support ring disposed to provide a brace against canting and other unwanted off-axis displacement, as formerly disclosed in previous art cited supra.

Rather, plunger 40 comprises integral support structure which provides open space for gas capture and yet added rigid support provided for communicating plunger rings against an associated internal syringe barrel wail. Those familiar with syringe fabrication art well understand effect of non-homogeneous surface friction distribution, knowing that a variance in such distribution, if not accounted and corrected for, can cause a plunger, which Is displaced only by fluid convnrunication, to cant (be angularly displaced relati ve to a long axis of a syringe barrel). Such canting can result in either unwanted communication between fluids in otherwise disparate chambers or misreading volumetric measurements made between indicia on barre! 60 and a predetermined measurement edge-site on plunger 40. C tingproteetlon

To guard against such canting, plunger 40 comprises a plurality of air-capturing holes, commonly numbered 1. 10 which are closed on a distal side (not shown), surrounded by a support structure 1 12 constructed to maintain a firm and compressive contact against an associated barrel 60 internal surface. Structure 1 12 also provides a make-up which maintains integrity of a tube 1 14 which surrounds and provides an entrance to fluid pathway 1 1 from a liquid only zone disposed within a fluid fulled chamber of barrel 60, While many different geometries can provide such support, structure which comprises the support structure about hollow cylinders is preferred.

An alternate plimger 40' is seen in Figure 3 A. While it is effective to reduce canting to an acceptable level using support structure 1 12 {seen in Figure 3 , holes 1 10 associated with such structure can harbor gas during a filling process. Such a gas refuge can be eliminated with a larger cone-shaped cavity 1 10' , However, cavity 11 ' yields a thinned wa!l 1 1 1 near a proximal ring 1 1. Γ. As rings, such as ring 1 1 Γ, are generally oversized relative to an interna! surface of a barrel, such as barrel 60 (see Figure 1), to assure sufficient compression to be fluid tight against the barrel, a variation in size of plunger rings can also be used to reduce canting. As an example, a distal ring 1 1 1" of plunger 40' can be oversized by four percent while ring 1 1 1' can be oversized by 6 six percent. Such variation in oversizing produces a compressive force in the region of ring 1 .1 which compensates for thinning. More details concerning delivery of onl liquid from the liquid only zone is provided hereafter.

Valve state, tarn

Reference is now made to Figures 4 and 5 wherein a stem 50 is disposed to close pathway 1 1 in Figure 4 to form a closed state of a plunger valve 70. Note that plunger valve 70 is in an open state in Figure 5 resulting from displacement of stem 50. Further note that, when plunger valve 70 is in a closed state (Figure 4), footing 94 is visible outside plunger 40 and section 100 is not seen. When plunger valve 70 is in an open state, stern 50 has sufficient length that section 100 is visible outside plunger 40 and footing 94 is hidden.

Knowledge of the state of plunger valve 70 is critical in determining validity of usefulness of dual-chamber syringe system 10. Display of footing 94, as seen in Figures 6-9 provides assuring evidence that no tampering or inadvertent valve actuation has occurred. For when footing 94 is so visible, plunger valve 70 is closed. Such Is the case in Figures 6-9.

To guard against premature opening of plunger valve 70, a removable sleeve 32, seen in Figures 7 and 8, provides a guard, when affixed to plunger rod 30. So affixed, a barrier is provided to prevent footing 94 being displaced into contact with barrel inner surface wall 120 resulting in such valve opening. With sleeve 32 in place, plunger rod 30 can be displaced arbitrarily without inadvertent plunger valve 70 displacement to a valve 70 open state. As is seen in Figure 1, sleeve 32 comprises opposing wings, commonly numbered 122, which, are "pinched" to spread attaching legs, commonly numbered 124, for removal from rod 30. Once sleeve 32 is removed reference for dual-chamber syringe 10 is changed herein to dual- chamber syringe 10'. Sleeve 32 can be made by extruding polypropylene.

Other than delinquent tampering, a plunger val ve 70 of a dual-chamber syringe system 1 ^* could be inadvertently and improperly triggered to an open state simply by premature displacement of stem 50 against in internal surface wall 120 of barrel 60 after safety sleeve 32 is removed. Displacement for triggering plunger valve 70 is seen in Figures 9 and 10, Note that sleeve 32 is no longer affixed to plunger stem 30. Note that such displacement is made evident by disappearance of footing 94, which is seen in Figure 9, but unseen in Figure 10. Also, section 100, being clearly visible as in Figure 10, indicates transition of plunger valve 70 to an. open state and is not seen in Figure 9. Of course, operation of dual-chamber syringe system 10' after premature opening of plunger valve 70 should be avoided and evidence of such is critical.

Proximal chambe considerations and obvia ion of gas delivery

For many purposes a dual-chamber syringe system 10 is delivered from a

manufacturer proximal chamber 80 being pre-fiiled (see Figure 8). Different from distal chamber 90 of system 10, gas is not easily purged from chamber 80 immediately prior to use. As seen in Figure 3, valve plunger 40 comprises tube 114 which has an entry orifice 126 set apart a predetermined distance from holes 1.10. Space within holes 1 10 and from holes 1 10 to just shori of orifice 126 is provided for accumulaiing gas which is kept away trom orifice 126 by physical material state properties thereby forming a liquid only zone, it is preferred that holes 1 10 be asymmetric l such that gas is not retained in the holes 1 10 when vertically oriented with hole 1 10 orifices open upwards. It should be recognized that only a limited volume of gas can be so retained. For this reason, a quality assurance procedure provides opportunity to confirm gas-free delivery and safety of system 10'. As seen in Figure 7, to perform quality control procedures during manufacturing and before use, a dual-chamber syringe system 10 ( or 1 '} is held upright and the relative level of a liquid/gas interface is determined to be above orifice 126, As seen in Figure 7, for safety, the gas liquid interface 140 resides above orifice 126 when system 10 (or 1 ') is so oriented. It should be noted that holes are but one alternative for providing space for collection of gas. As an example, a shallow cavity which permits the same space as the volume of gas which can be resident in hoies 1 10 can be used within the scope of the invention.

Further, it should be noted that gas within the pathway associated with orifice 126 should be cleared of gas by the filler (e.g. manufacturer) at the time of filling. Due to the liquid only zone, no further consideration need be given to gas resident in the pathway.

However, when fiiling chamber 90, care should be taken to purge gas from all parts of chamber 90 including the distal portion of the pathway associated with orifice 126. Such care is generally performed for purging gas from filled conventional syringes before dispensing,

Filling an dis osing the dual-chamber syringe

Sleeve 32 should be retained in place while chamber 90 is being filled. Generally, a fluid 142 is drawn into barrel 60 by displacing plunger rod 30 in direction of arrow 144. Once a fluid 94 Is resident In chamber 90, sleeve 32 can be removed, as seen in Figure 6. Dispensing of fluid 94 from chamber 90 is accomplished by displacing plunger rod 30 in direction of arrow 146. As seen in Figure 9, near the end of chamber 90 dispensing cycle, looting 94 collides with syringe inner surface 120, As footing 94 is further displaced, chamber 90 is fully emptied. As seen in Figure 10, at the end of a chamber 90 dispensing cycle, footing 94 is no longer visible and section 100 provides an indicator for a plunger valve open state, ready for flushing delivery from chamber 80.

Guard against reflu ive flow at the end of a flushing cycle

Continued displacement of plunger rod 30 in direction of arrow 146, as seen in Figure 1 1, dispenses flushing liquid. It is important to consider the state of system 10' at the end of the flushing cycle. First, it is important to note that the flushing cycle should be terminated before any gas has been dispensed from chamber 80. Of equal concern is that, at the end of a chamber 80 dispensing cycle, any refluxtve flow back into system 10^! is undesirable, it is common knowledge to those skilled in patient care that such flow can produce an unsafe condition for an interconnected patient (e.g. through a catheter). In system 1 ', there are two methods for obviating refluxtve flow. A first method involves reintroducing bulbous portion 96 into a sealing state within pathway 1 16. (see Figures 4 and 5) by displacing plunger tip 20 against section 100 of stem 50 However, length of stem 50 may not effect ^introduction of portion 96 sufficiently to close plunger valve 70.

A second and preferred method is by providing a "hard" stop against continued displacement of plunger rod 30 and associated tip 20, It may be noted that gas within chamber 80 at the end of a flushing cycle has a sufficiently high pressure to assure continued dispensing at a moment when displacement of plunger 30 ends, However, if there is any concurrent reflexive action, such as may occur due to resiliency of tip 20 against stem 50 at section 100, dynamics of such reflexive action are generally slower than pressure reduction in gas in chamber 80. As such reflexive action is counter to direction of plunger rod 30 displacement and slower than chamber 80 pressure reduction, the result being a .material volumetric displacement which produces refluxive flow.

For this reason, system 10' preferably employs a hard stop. Such a hard stop is provided in system 10' by a collision between a shoulder 150 strategically disposed as an outwardly extending part 151 of plunger rod 30 and a flanged proximal portion 152 of barrel 60, as seen in f igure 11. Such a hard stop, without reflexive motion has proved to take ad vantage of pressure resident in gas in chamber 80 to produce a limi ted amount of dispensing flow at the end of a flushing cycle which would not otherwise occur should there be a reflexive response.

hidida..ait.grx¾ati¥.aa

Volumetric measurement of fluid dispensed from a dual-chamber syringe, such as syringe 10', produces needs tor indicia presentation previously not required for single chamber syringes. As may e noted in Figures 6 and 9, regions along barrel 60 (of syringe 10') have different starting points and delivery sectors for fluid dispensed from each chamber 80 and 90. For purposes of this discussion, distal chamber 90 shall be considered to be a drug delivery chamber and proximal chamber SO shall be considered to be a flush delivery chamber. One exemplary pattern of indicia is provided in each Figure 12 and Figure 13. A first item to note is that all of the effective measurement indica, generally numbered 200 in Figure 13, are disposed at a distal end of barrel 60. Referring to Figure 1.2, it may be noted thai separate measurement lines, identified as 210 and 220. are provided for contents of each chamber 80 (dose fluid) and chamber 90 (flush), respectively. Of necessity, due to sequential delivery of system 10' contents and space required for plunger valve 70 and a gas safety reservoir, indicia scales (2 Ϊ 0 and 220) and related numbers are offset and overlapping.

Similarly,, there is an overlapping pattern seen in Figure 13. However, common indicia lines 230 are provided for both drug and flush metering. A separate set of numerical measurement indicators (240 and 250) is provided for differentiating metering of dose and flush, respectively.

An advantage of indicia layout in Figure 12 is that the two sets of indicia for dose and flush are entirely separate. As such, flush indicia 220 are not required to have a line-to-lme correspondence and better use of available barrel 60 space than for the pattern of indicia in Figure 13, results. A marked advantage of indicia layout in Figure 13 is the provision for use of common indicia lines. Another consideration one must take into consideration is a likelihood of confusion about indicia used for measurement of drug or flush (i.e. that which is effective during each system 10' dispensing cycle). For this purpose, it h recommended that color differentiation be provided to differentiate dispensing of contents from chambers 80 and 90, as seen in Figure 12.

Still another consideration for indicia patterns, seen in Figures 12 and 13, is that, line indicia are not required along the length of barrel 60 as is commonly the case in conventional syringes. Generally the most proximal Sine along a conventional barrel is also an indicator for limiting proximal displacement of a plunger rod and associated tip. For this purpose, a limit line 260 is provided as seen in each Figure 12 and 13. it should be noted that basic ad vantage for patterns seen in Figures 1.2 and 13 is that measurement of volumes in. each chamber is independent of fluid quantities in the other chamber. However, use of these patterns does require a change of plunger reference when switching from dispensing from one chamber to another. It is well known that conventional single chamber syringes have a dead space (volume of undeliverable fluid) disposed in the space between the barrel and distal end of the male filer fitting. As such does not exist In a distal chamber of a dual-chamber syringe (due to distal chamber Hushing following dispensing from the distal chamber), a correcting offset in an associated indicia pattern is required for delivery of otherwise undispensed, fluid.

If it is preferred to measure all dispensed volumes by reference to a single plunger (such as plunger tip 20 (see figure 1 ), indicia seen in Figures 13 A- 13E may be erapioyed. in Figure 13 A, indicia pattern 270 comprises a single linear line of volumetric measurement marks and descriptors 272 and 274 for dose and flush, respectively, it is important to note that for a single linear line of volumetric measurement lines to be used, the linear distance between plunger tip 20 and plunger valve must be of known predetermined length and held constant in all such dual-chamber swinges 10'. Such is true for all indicia seen in Figures 13B - 13 D, as well, in the case of measurement being made by displacement of plunger rod 30, measurement Is made at the interface between syringe barrel flange 152 and a respective coi nciding mark of indicia pattern 270 on stem of rod 30.

As seen in Figures 13B - I3E, a set of indicia lines 280, comprise a single linear line of marks for both dose and flush. In this case, the distal edge of plunger tip 20 provides the measurement reference line (as is the case for single chamber syringes). Note that dose (282) and flush (284) patterns are reversed on indicia of Figure 13B compared to indicia of Figure 13 A. Note also that there is a blank region 286 where no indicia is printed. Region 286 represents space for plunger volume and fluid (liquid and gas) residual in chamber 80. Since plunger tip 20 is restricted from further displacement by contact of shoulder 150 with flange 152 (see Figure 1 E) no volumetric measurement is required in region 286.

Dispensing steps are seen in sequence in Figures 13B to Figure 13E. A syringe 10' comprises filled chambers 80 and 90 for a twenty mi dose in Figure 13C and a 10 ml dose in Figure 13C. No markings denoting fluid (gas or liquid) content in barrel 60 is provided to guard against confusion with indicia marks. In Figure 13D, all dose, except that contained in dead space in the throat 290 of barrel 60, is dispensed. In Figure 13E, liquid in chamber 80 is dispensed along with dose remaining in throat 290,

Still another indicia pattern is seen in Figure 13F, As it may be preferable to fill and measure volumes in chamber 90 using the most distal plunger (plunger valve 40), a set of indicia numbers (generally referenced by 292) are provided as seen on the left side of barrel 60. Later, when dispensing a set of indicia numbers (generally referenced by 294) are provided as seen on the right side of barrel 60. !t should be noted that use of indicia 292 pro vides a direct and accurate measure for volumetric measurement of fluid in chamber 90, while use of indicia 294 provides a measurement independent of canting of plunger valve 40,

As system 10 can he delivered as a dual-chamber syringe with one chamber pre-fif led. it is recommended that all parts used in system 1 be compatible with gamma sterilization. Tapered Valve Fittings for Closed System Operation

One of the major applications for dual-chamber syri nge systems is in dispensing oncology drugs where need for a closed system is preeminent. Of course, oncology uses are not the only applications for dual-chamber syringe systems, but the toxic nature of oncology drugs has produced a significant impetus for the development of closed systems.

Reference is now made to Figures 14-35 wherein a valve for tapered fittings is disclosed. As seen in Figure 14, a valve 300, made according to the instant invention, is seen. Valve 300 comprises four separate sections, an eliipticaliy shaped slit valve 310, a transition section 320 and a circularly shaped portion 330. For a valve 300 to be used with a female tapered liter fitting, each section comprises a 3° taper. Similar to a back-to-back valve disclosed in Thome 681, slit valve 300 comprises an internal cavity disposed to provide a closing force upon medially disposed silt 340 when acted upon by internal syringe pressure. The cavity portion of valve 300 is part of baek-to- back. valving which is only opened by compressing slit valve 300, preferably into a circular shape. Further, as in ah the art from which this U.S. Patent Application continues, s t 340 is medially disposed, in this case along a major axis 342 of an elliptical face 344 of valve 300, Due to very limited space available within a luer fitting and a need for a cavity whereby fluid pressure within the valve compresses slit 340 to obviate syringe dispensing flow, a .medially disposed slit 340, see in f igure 14, the space for both a cavity and adequate wall thickness in the region of the cavit is not adequate for a reasonable design.

To accrue a better utilization of available space within dictates of luer fitting

dimensions, a different slit valve 400, seen in Figure 15, valve 400 comprises similar sections to valve 300 comprising an ellipticaily shaped slit valve actuator 410, a transition section 420 and a circularly shaped portion 430. However, in valve 400, a slit 440 i offset from a major elliptical axis 442, indicated by a dashed l ine 444. As is clarified hereafter, establishing slit dimensions, which determines a hole diameter which is formed by compress! vely deforming elliptical val ve parts to circular parts which conform to a female luer fitting into which valve 400 is inserted, also can be used to determine major and minor axis dimensions of va!ve 400 with an offset slit, as disclosed hereafter.

Reference is now made to Figure 16. Valve actuator 410 comprises a dista! part 450 and proximal part 460. Extremities of parts 450 and 460 are distinguished by cross-cutting planes 462, 464 and 466. Plane 462 is disposed across a face 468. Plane 464 is disposed between parts 450 and 460. Plane 466 is disposed at the most proximal extremit of part 460. A slit 440 is disposed offset from a major axis (not shown) of an ellipse 469 at the plane 462 of face 468,

Valve 440 is seen in a side cross-cut view in Figure 17. Part 450 is seen to be solid, except for slit 440. Part 460 comprises both a cavity 4S0 and slit 440. As mentioned supra, cavity 480 permits pressurized fluid to be applied orthogonal to the plane of slit 440 effecting closure when valve 440 is not compressively opened by insertion into a tapered fitting. A wide collar 481 is disposed on a proximal end of valve 440 for sealing installation as disclosed hereafter.

A cross section of part 460 in plane 466 { see dashed line 470 in Figure 17) is seen in Figure 17A. Disposition of slit 440 below cavity 480 (and an associated major elliptical axis permits a wider wail thickness, indicated by numbers 482 and 484 than possible if slit 440 is disposed on the major axis).

Referring once more to Figure 17, a valve 400 comprises a hole 490 which is closed internally at plane 466 (see Figure 16) which is the proximal end of valve actuator 410. As material from which valve 400 is made must be supple to be compressed to open slit 440 and must be rigid enough to be effectively fully inserted into a tapered female fitting, an inner skeletal support is needed. As seen in Figure 25_» such a skeletal support 500, preferably inj ection molded of syringe compatible polypropylene, is sized and shaped to fit snugly within hole 490. As better seen in Figure 26, support 500 comprises distal extensions, general ly numbered 502, at the end of a support member 504. A collar 506 is provided for assembly support. A thru hole 510 provides a fluid communication pathway. Distal extensions 502 provide skeletal support for inserting valve actuator 410 while also providing a space for a fluid, pathway for an opened slit 440 to cavity 480. An end-on view of support 500 is seen in Figure 27.

A cross section, in the plane of slit 440 is seen in Figure 24 to comprise a skeletal support 500 and a valve 400 which combine to provide an msertable valve 600. Unless valve 400 can be made with sufficient rigidity to be self-supporting, skeletal support 500 should be provided. As disclosed hereafter, such support may be provided by aa associated housing.

Reference is now made to Figures 18-23 which provide comparisons between closed and open slits. Seen in Figure 18 is a closed slit disposed across plane 462; similarly, Figures 19 and 20 disclose closed slits associated with planes 464 and 466, respectively. Figures 21 - 23 are disposed in the same planes as Figures 18-20, respectively. Compressing valve actuator 410 within a circular tapered fitting results in val ve 400 being opened as seen in Figures 21-23. Note thai volume of cavity 480 is reduced while a through hole 602 is opened. Due to physical material constraints, hole 602 may not be round, but have acute lip

separations at slit ends, generally numbered 604. For this reason, slit 440 should he lengthened beyond pi times desired hole diameter.

An insertable valve according to the instant inventio may be assembled as a standalone male adapter 700 from three parts. As seen in Figures 28 and 29, male adapter 700 comprises a valve 400, a male luer lock fitting 702 and a female luer lock fitting 704. Female fitting 704 comprises a integrally molded skeletal support 706 (which is consistent in form and function with skeletal support 500 seen in Figures 24-26.

For syringe applications, a conventional syringe barrel, such as barrel 60 (see Figure 1), can be modified to provide a skeletal support, as seen in Figures 30 and 33. As best seen i Figure 33, rather than a conventional male luer fitting, barrel 60' comprises a skeletal support 706^* which, like support 706 (see Figures 28 and 29) is consistent in form and function with skeletal support 500 seen in Figures 24-26. Assembly of a dual-chamber syringe with an associated valve 400 is seen in Figures 30-32. A valve 400, seen separate in Figure 30, is disposed about skeletal support 706' as seen in Figur s 31 and 34. A compression ring 710, designed to be inserted eompressiveiy to provide a fluid seal about support 706', provides for a seal and physical containment of valve 400.

As can be seen in Figures 30-32, a plunger valve 40 disposed in barrel 60' converts a single barrel syringe into a dual-chamber syringe 10", which provides closed system operation, with a valve only opening when inserted into a female luer fitting. One skilled in medical swinge art well understands that, similarly, a single chamber swinge having a barrel 60^* without a chamber dividing plunger valve would have similar closed system qualities.

Critical parameters tor bui lding a model for a valve 400 can be calculated as provided hereafter. As an example, if a hole radius (R) is desired, a slit length (L) would be:

L ^:::: pi * ( )

However, as disclosed supra, for a given hole diameter, the slit length should be lengthened to account for lip separation 604 anomalies (See Figures 21 - 23). As an example, for a hole diameter of ,055 inches, adding five percent to the length increases the slit length from .086 to .091.

Offsetting slit 440 (see Figure 15) b twenty thousandths is preferred; however other offsetting amoun ts can be made within the scop of the instant in ven tion. Once the sli t l ength (hole size) and effective slit lengthening and offset are determined, it is recommended that ISO specifications be followed for calculating valve 400 design parameters. The following table 1 summarizes contemporary ISO specifications. It should be remembered that these specifications are provided for single chamber syringes. inches

Male luer length .295

Female luer length .295

Insertion variance .159

Maximum engagement length .159

Maximum insertion length .226

Male end diameter ,154 Female insertion diameter , 159

Male diameter at end .156

Variance of male fitting .002

Fitting taper 3%

Table ! - Current Applicable ISO Specifications

For an eHipticaiiy formed valve, the only critical specifications are major and minor elliptical axes, insertion depth and associated fitting dimensions (diameter) at that depth and valve length. In the case of the current example, the desired parameters are

! . Fitting radius, i.e. at distal face 468 of inserted valve (r): .077 inches

2. Circumference at face 468 (C) .485

3. Slit offset (from major axis) (O) .020

4. Length of inside female fitting chord at slit offset (F) .149

5. Precompression length of valve at slit (P) .180

Given the above listed parameters, a value for a half major axis (A) can be caieulated by the following:

The tangent (T) o an angle defined by a base of precompression length (P) and slit offset (O) is given by:

T - G/P

The angle (0) associated with "T" is:

Θ ^::: aretan (T) An estimate for A is preferably calculated by:

A - F/(eos Θ) - .093 inches Noting that calculated A, whi le close to a tme value of the major axis is not exactly so, a value for the minor half axis (B) of the associated ellipse can be approximated from a known area (a) of the inner surface of the female fitting. Noting that desired area (a) is area of the fitting less area of hole which equals pi times R squared. Thus:

a - pi( - R²) and an estimated value for 8 is

estimated B ~ a/(pi A) ~ .058 inches

However, aoting that both A and B are estimates, a check on the value of B by calculating circumference of the associated ellipse shows that a correction o +.002 to B decreases an error in circumference comparing circumference of the associated ellipse to the circumference of the fitting to less than .2 percent. With A and B and slit length so determined, a cavity with a maximum width of .020 provides all of the necessary dimensions to fabricate a valve actuator 410 (see Figures 15 and 16) which is , 100 inches long.

It should be noted that major axis (2 A) being .186 inches long requires filleting 467 of the face 468 for facile insertion. Also, transition geometry within transition section 420 (See Figure 15) should be linear- to retain corresponding circumference between the associated female fitting and exterior surface of valve 400.

Systems Kit for Step Reduction

Reference is now made to Figure 36 wherein a system 1.0 and a pre-filled female luer fitting syringe 800 are seen. Note that system 10 comprises a male liter fitting 81.0 and syringe 800 comprises a iemaie luer fitting 820. Syringe 800 is a single chamber syringe pre- filled with a dose 830 destined to be dispensed into distal chamber 90 of system 10. It should be noted that syringe 800 may be specially made for storage of dose 830 (e.g. made from glass). Transferring dose 830 into chamber 90 of system 1.0 is accomplished by a single luer fitting connecting step thus eliminating other commonly used components, such as male/mate connectors. By reducing system 10 filling to a single connection, problems, such as those associated with nosocomial infections, are reduced.

Conclusion Inventions disclosed herein may he embodied in other specific forms without departing from the spirit or essential characteristics thereof. The present embodiments are therefore to be considered in all respects as illustrative and not restrictive, the scope of the inventions being indicated by the appended claims rather than by the foregoing description, and all changes which come within the meaning and range of equivalency of the claims are therefore intended to be embraced therein.

What is claimed and desired to be secured by Letters Patent is:

Claims

The Claims:

1 (Original) A dual-chamber syringe system comprising:

a dual-chamber syringe comprising a medical syringe having a conventional hollow syringe barrel which comprises a hollow, substantial ly constant diameter inner wall, a distal end at which a distal chamber is filled and a proximal end which comprises a flanged opening sized and shaped for plunger introduction;

said syringe also comprising a plunger rod and associated plunger tip which is disposed within said barrel for the purpose of displacing fluid therein;

said dual-chamber syringe further being characterized by a plunger valve which is disposed to divide said barrel into two disparate chambers, a distal chamber which is disposed between said plunger valve and said distal end and proximal chamber which is disposed between said plunger valve and said plunger tip, said proximal chamber being pre-filled with fluid which is dispensed only upon completion of a dispensing cycle of fluid from the distal chamber and said plunger valve being displaced only by force of fluid communicating with said plunger rod and associated lunger tip;

said plunger valve being characterized by a valve plunger comprising an interfacing cylindrical outer wall which compressiveiy wipes against said barrel inner wall to maintain disparity between the distal and proximal chambers and a fluid pathway tube between the proximal and distal chambers which is closed until fluid within the distal chamber is fully dispensed and further comprisin integral structure disposed about said tube to compressiveiy interface with said barrel inner wall to assure no fluid flow between said inner wall and said cylindrical outer wall and to keep said valve plunger from canting when displaced by only the liquid communication within said barrel thereby assuring maintenance of disparity between chambers when said plunger valve is closed and accuracy of measurement when said plunger valve is displaced and visually monitored for volume measurement;

said system being characterized by a visible indicator for valve and system readiness status for tire purpose of avoiding use after inappropriate system handling due to a group of causes comprising tampering and inadvertent premature valve actuation;

said dual-chamber syringe further being characterized by a stop actuated at the end of a proximal chamber dispensing cycle which is effective in producmg no refJuxive flow; and said system further being characterized by a pattern of indicia which clearly

communicates volumetric measurement status for each distal and proximal chamber dispensing cycle.

2. (Original) A dual-chamber syringe system according to Claim 1 wherein said plunger valve is characterized by a displaceable valve stem comprising a distal footing which is visible only when said plunger valve is closed to provide a closed valve indicator and a proximal plunger valve stem section which is visible only when the valve is opened to provide art indicator of an open valve thereby providing said visible indicator.

3. (Original) A dual-chamber syringe system according to Claim 2 wherein said system is characterized by a removable sleeve affixed to said plunger rod to retard said rod from full being displaced into said barrel and thereby impede premature displacement of said stem and resultant actuation of said plunger valve.

4. (Original) A dual-chamber swinge system according to Claim 1 wherein said proximal chamber is characterized by fluid comprising liquid and a predetermined maximum volume of air which should not be dispensed and said plunger valve pathway comprises an extended tube into a liquid only zone whereby only liquid is dispensed from the proximal chamber.

5. (Original) A dual-chamber swinge system according to Claim 4 further

characterized, by a. gas volume measurement by which assurance is provided that no air can b dispensed from the proximal chamber,

6. (Original) A dual-chamber syringe system according to Claim 1 wherein said plunger rod is characterized by a shoulder disposed to provide a hard stop upon impact against said Hanged opening to thereby deter refluxive flow at the end of a proximal chamber dispensing cycle.

7. (Original) A dual-chamber syringe system according to Claim 1 characterized by measurement indicia patterned for separately measuring each chamber, said Indicia comprising a first set of indicia for monitoring displacement of said valve plunger while dispensing fluid from said distal chamber and a second set, of indicia for monitoring

displacement of said plunger tip while dispensing fluid from said proximal chamber.

8. (Original) A dual -chamber syringe system accordmg to Claim 7 wherein said first and second sets are characterized by over-lapping indicia.

9. (Original) A dual-chamber swinge system according to Claim 1 characterized by measurement indicia patterned for measurement by a single displacing element.

10, (Original) A dual-chamber syringe system according to Claim 9 wherein the displacing element is said plunger rod which is characterized by a pattern of Indicia disposed thereon.

1 1 , (Original} A dual-chamber syringe system according to Claim 9 wherein the displacing dement is said plunger tip and said barrel is characterized by a single pattern of lines with a section of said pattern for measuring dispensing from said distal chamber and a contiguous section for measuring dispensing i om said proximal chamber.

12, (Original) A dual-chamber syringe system according to Claim 1 wherein said integral structure is characterized by solid wall construction perforated by at lest one of dead- ended hole, thereby providing space for collection of gas about said tube while providing support structure for said cylindrical outer wall.

13, (Original) A dual-chamber syringe system kit according to Claim I further being characterized by a female luer syringe containing fluid to be drawn into said dual-chamber syringe, said dual-chamber syringe barrel being characterized by a male luer syringe such that fluid transfer is accomplished by a single male to female luer fitting connection.

14, (Original) A dual-chamber syringe system according to Claim 1 wherein said barrel is characterized by a skeletal support for a tapered fitting valve.

15. (Original) A syringe comprising a syringe barrel having a distal end whereat fluid is drawn into said barrel and dispensed therefrom, said end being characterized by an integrally molded skeletal support for a tapered valve,

16. (Original) A valve for a tapered fitting, said valve being characterized by:

a distal valve actuating section being characterized by an asymmetric tapered exterior wail and a slit there through;

a proximal section being characterized by an exterior wall which conforms in size and shape to an associated portion of the tapered fitting into which said valve is inserted to be actuated; and

a transition section disposed between said distal and proximal sections;

sizing and shaping of all sections such that whe said valve is inserted into the tapered fitting corresponding surfaces of the valve and tapered fitting being characterized by having substantially the same circumference;

said distal valve actuating section being characterized by back-to-back valves which are closed when said valve is not inserted and ope by compression upon insertion into an appropriately sized tapered fitting,

17. (Original) A valve for a tapered fitting according to Claim 1 wherein said exterior wall is characterized by shape of an ellipse comprising a major and a minor axis.

18. (Original) A valve for a tapered fitting according to Claim 17 herei said slit is characterized by being parallel to, but offset from, said major axis.

19, (Original) A valve for a tapered fitting according to Claim 16 wherein said distal valve actuating section is characterized by a distal portion and a proximal portion.

20. (Original) A val ve for a tapered fitting according to Claim 1.9 wherein said actuating section comprises a distal portion is characterized by a solid except for said slit as a first of said two back-to-back valves and a proximal portion as a second of said two back-to- back valves being characterized by a cavity whereby fluid pressure internal to said valve is exerted about said slit to maintain said proximal portion closed unless said exterior wal l is distorted, such distortio opening both distal and proxima! valve actuating portions.